DNA-binding protein

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Cro protein complex with DNA
Interaction of DNA (orange) with histones (blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.
The lambda repressor helix-turn-helix transcription factor bound to its DNA target[1]
The restriction enzyme EcoRV (green) in a complex with its substrate DNA[2]

DNA-binding proteins are

B-DNA, because it exposes more functional groups that identify a base pair.[6][7]

Examples

DNA-binding

transcription activator like effectors
.

Non-specific DNA-protein interactions

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called

Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[11] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[12] Other non-specific DNA-binding proteins in chromatin include the high-mobility group (HMG) proteins, which bind to bent or distorted DNA.[13] Biophysical studies show that these architectural HMG proteins bind, bend and loop DNA to perform its biological functions.[14][15] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that form chromosomes.[16] Recently FK506 binding protein 25 (FBP25) was also shown to non-specifically bind to DNA which helps in DNA repair. [17]

Proteins that specifically bind single-stranded DNA

Further information: Single-stranded binding protein

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[18] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

Binding to specific DNA sequences

DNA contacts of different types of DNA-binding domains from transcription factors

In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[19] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.[20]

These DNA targets can occur throughout an organism's genome. Thus, changes in the activity of one type of transcription factor can affect thousands of genes.[21] Thus, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to read the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[22] Mathematical descriptions of protein-DNA binding taking into account sequence-specificity, and competitive and cooperative binding of proteins of different types are usually performed with the help of the lattice models.[23] Computational methods to identify the DNA binding sequence specificity have been proposed to make a good use of the abundant sequence data in the post-genomic era.[24]

Protein–DNA interactions

Protein–DNA interactions occur when a

histones that form part of the structure of DNA and bind to it less specifically. Also proteins that repair DNA such as uracil-DNA glycosylase
interact closely with it.

In general, proteins bind to DNA in the

major groove; however, there are exceptions.[25] Protein–DNA interaction are of mainly two types, either specific interaction, or non-specific interaction. Recent single-molecule experiments showed that DNA binding proteins undergo of rapid rebinding in order to bind in correct orientation for recognizing the target site.[26]

Design

Designing DNA-binding proteins that have a specified DNA-binding site has been an important goal for biotechnology.

type III secretion system when they infect various plant species.[27]

Detection methods

There are many in vitro and in vivo techniques which are useful in detecting DNA-Protein Interactions. The following lists some methods currently in use:

ChIP-chip. Yeast one-hybrid System (Y1H) is used to identify which protein binds to a particular DNA fragment. Bacterial one-hybrid system (B1H) is used to identify which protein binds to a particular DNA fragment. Structure determination using X-ray crystallography
has been used to give a highly detailed atomic view of protein–DNA interactions. Besides these methods, other techniques such as SELEX, PBM (protein binding microarrays), DNA microarray screens, DamID, FAIRE or more recently DAP-seq are used in the laboratory to investigate DNA-protein interaction in vivo and in vitro.

Manipulating the interactions

The protein–DNA interactions can be modulated using stimuli like ionic strength of the buffer, macromolecular crowding,[26] temperature, pH and electric field. This can lead to reversible dissociation/association of the protein–DNA complex.[36][37]

See also

References

  1. ^ Created from PDB 1LMB
  2. ^ Created from PDB 1RVA
  3. ISBN 978-0-412-25990-6
    .
  4. PMID 6236744
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  5. doi:10.1038/scientificamerican1283-94
    .
  6. PMID 2422697
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  7. PMID 2421408
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  8. S2CID 21101836
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  9. PMID 15853876
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  10. S2CID 4328827
    .
  11. S2CID 1883924
    .
  12. PMID 12596902. {{cite book}}: |journal= ignored (help
    )
  13. PMID 11497996
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  14. PMID 25063301
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  15. PMID 28303166
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  16. PMID 8178371
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  17. PMID 26762975
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  18. PMID 10473346
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  19. PMID 10966474
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  20. S2CID 14668705
    .
  21. PMID 12808131
    .
  22. PMID 6236744
    .
  23. S2CID 103345
    .
  24. PMID 23814189
    .
  25. PMID 9646864
    .
  26. ^
    PMID 27471033
    .
  27. PMID 21929364
    .
  28. S2CID 310256
    .
  29. PMID 6275366
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  30. PMID 6269071
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  31. PMID 21108821
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  32. PMID 27557760
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  33. PMID 26025051
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  35. PMID 212715
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  36. doi:10.1002/elan.200904566
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  37. PMID 27874042
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External links
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